U.S. Pat. No. 7,030,158 discloses N-(all-trans-retinoyl)-L-cysteic acid methyl ester and N-(13-cis-retinoyl)-L-cysteic acid methyl ester. These compounds are produced by dissolving all-trans- or 13-cis-retinoic acid and triethylamine in anhydrous tetrahydrofuran, and thereafter adding acetonitrile and butyl chloroformate. After some time the obtained mixture is added to a solution of a derivative of L-cysteic acid, sodium bicarbonate, methanol, tetrahydrofuran and water. Hence, the formation of N-(13-cis-retinoyl)-L-cysteic acid methyl ester and/or N-(all-trans-retinoyl)-L-cysteic acid methyl ester is not carried out in a single phase.
It is an object of the present invention to further decrease complexity and to further simplify the process to form N-(13-cis-retinoyl)-cysteic acid alkyl ester and N-(all-trans-retinoyl)-cysteic acid alkyl ester.
A further object with the present invention is to further increase the yield. Also, the present invention significantly reduces the reaction time as a function of yield, alternatively, provides an increased yield at comparable reaction times.